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目的 探讨不同修饰的反义寡核苷酸 (ODN)抑制胆管癌细胞血管内皮生长因子 (vascularendothelialgrowthfactor,VEGF)基因表达的效应。 方法 将 4种不同修饰的反义VEGFODN分别加入胆管癌细胞中 ,用RT PCR及免疫组织化学技术检测胆管癌细胞中VEGFmRNA及蛋白表达 ,同时测定各上清液刺激血管内皮细胞生长的受抑情况。结果 反义VEGFODN明显抑制胆管癌细胞VEGF基因及蛋白的表达 ,其中以硫代修饰的ODN3抑制作用最强 ,在 10、2 0 μmol/LODN作用下 ,其抑制增殖效应为(0 .690± 0 .0 16) ,(0 .688±0 .0 10 )。结论 反义VEGFODN有望成为胆管癌基因治疗的较理想药物之一。
Objective To investigate the effect of different modified antisense oligonucleotides (ODNs) on the gene expression of vascular endothelial growth factor (VEGF) in human cholangiocarcinoma. Methods Four different antisense VEGF ODNs were added to cholangiocarcinoma cells respectively. The expression of VEGF mRNA and protein in cholangiocarcinoma cells was detected by RT-PCR and immunohistochemistry, and the inhibitory effect of each supernatant on the growth of vascular endothelial cells . Results Antisense VEGF ODN significantly inhibited the expression of VEGF gene and protein in cholangiocarcinoma cells. Among them, the thio-modified ODN3 had the strongest inhibitory effect, and the inhibitory effect of ODN3 at 10,2 0 μmol / L ODN was (.690 ± 0 .0 16), (0 .688 ± 0 .0 10). Conclusion Antisense VEGFODN is expected to be one of the more ideal drugs for gene therapy of cholangiocarcinoma.